Neural activity from receptors in the anterior tongue gives rise to a gustatory message that reflects the activation of both the taste and trigeminal somatosensory pathways. Currently not understood, and is the focus of this application, are the peripheral and central mechanisms regarding how the trigeminal (TG) system influences the taste system. The overall goals in this proposal are (1) to determine how compounds that activate TG neurons can modulate responses evoked from taste receptors cells (TRCs) and chorda tympani (CT) neurons, and (2) to quantify the contributions of the trigeminal somatosensory (mechanosenosry and nociceptive) pathways to the encoding of gustatory information in the insular cortex. It is proposed that, when activated, TG neurons will release neuropeptides, such as substance P and CCK, that will bind to receptors on TRCs and thereby modulate them. That in turn will modulate the activity of CT neurons to lingual applications of NaCl, acid, sucrose, and quinine. This hypothesis will be tested by activating the TG nerve electrically and chemically (e.g., with capsaicin, the pungent ingredient in hot pepper) and also by comparing CT responses before during and after the system injection of agonists and antagonists of substance P and CCK. A variety of methods (RT-PCR, immunocytochemistry, patch clamp, and measuring changes in intracellular calcium) will be used to determine whether CT modulation by TG activators such as capsaicin, is direct (on TRCs) and/or indirect via peptide release. Emphasis will be on identifying receptors for neuropeptides, capsaicin (VR1), and proton-gated channels in TRCs, lingual epithelium and geniculate ganglion neurons. To quantify the contribution of the TG somatosenory pathways to the cortical encoding of gustatory information, bundles of microelectrodes will be implanted in the primary gustatory (insular) cortex. Then, in lightly anesthetized rats, the simultaneous responses of populations of single insular neurons to a set of standard tastants will be measured before and after the selective inactivation of TG ganglion innervating the anterior tongue, a procedure that will simulate lingual nerve injuries. In addition, cortical-cortical influences on gustatory coding will be tested by reversibly inactivating the primary somatosensory cortex (SI). Information obtained from both the peripheral and cortical recordings will provide novel molecular, cellular and circuit mechanisms regarding the modulation of sensory information, and quantitative information regarding the contributions of the TG system to gustatory coding.